title: Evaluation of canine T-cell dependent antibody response to the primary and secondary immunization with keyhole limpet hemocyanin.
abstract: T-cell dependent antibody response (TDAR) incorporating both primary and secondary responses to keyhole limpet hemocyanin (KLH) in canine models have not yet been fully understood. To develop a practical dog TDAR model, we characterized primary and secondary antibody responses by intravenous or intramuscular immunization of KLH twice at intervals of 8 days during a 28-day course of study. Primary immunization with KLH by both routes induced a maximum IgM response on 6 to 8 days after the treatment, whereas the IgG response started 6 to 8 days after the treatment with relatively low levels. Remarkable increases in anti-KLH IgG levels (about 10-times compared with the primary response) were produced 5 to 7 days after the secondary KLH immunization by both routes. These results indicate that IgM-predominant and IgG-predominant responses were respectively induced by the primary and secondary immunization. Furthermore, the intravenous route showed higher baseline titers of primary and secondary anti-KLH IgM responses, suggesting that intravenous immunization of KLH might be a more suitable method for immunotoxicity evaluation. No remarkable inter-individual variability was noted in our canine models. Treatment with cyclophosphamide at 2 mg/kg/day for a consecutive 28 days significantly suppressed primary and secondary anti-KLH IgM and IgG responses induced by KLH injection on Days 15 and 23 of CPA treatment. These results demonstrate that these experimental designs could provide valuable information about the influence on both the primary and secondary humoral immune responses in dogs when exposed to potential immunomodulatory drugs.
authors.affiliation: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Japan. kawai.ryota.jn@daiichisankyo.co.jp
authors.forename: Ryota
authors.initials: R
authors.lastname: Kawai
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Aida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hattori
authors.forename: Tadashi
authors.initials: T
authors.lastname: Furukawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Mori
authors.forename: Wataru
authors.initials: W
authors.lastname: Takasaki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin